Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations

https://portalciencia.ull.es/documentos/64860111a219857f1d78a011

Detalles Bibliográficos
Autores: González Carracedo, Mario Andrés, Martín González, Elena, Hernández Pérez, José M., Pérez Pérez, José A., Pérez García, Javier, Herrera Luis, Esther, González Pérez, Ruperto, González González, Orelvis, Mederos Luis, Elena, Sánchez Machín, Inmaculada, Poza Guedes, Paloma, Sardón, Olaia, Corcuera, Paula, Cruz, María J., González Barcala, Francisco J., Martínez Rivera, Carlos, Mullol, Joaquim, Muñoz, Xavier, Olaguibel, José M., Plaza, Vicente, Quirce, Santiago, Valero, Antonio, Sastre, Joaquín, Korta Murua, Javier, Pozo, Victoria del, Lorenzo Díaz, Fabián, Villar, Jesús, Pino Yanes, María
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de La Laguna (ULL)
Repositorio:RIULL. Repositorio Institucional de la Universidad de La Laguna
OAI Identifier:oai:riull.ull.es:915/41776
Acceso en línea:http://riull.ull.es/xmlui/handle/915/41776
Access Level:acceso abierto
Palabra clave:Asthma
Exacerbations
SERPINA1
Alpha-1 antitrypsin
Alpha-1 antitrypsin deficiency
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spelling Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbationsGonzález Carracedo, Mario AndrésMartín González, ElenaHernández Pérez, José M.Pérez Pérez, José A.Pérez García, JavierHerrera Luis, EstherGonzález Pérez, RupertoGonzález González, OrelvisMederos Luis, ElenaSánchez Machín, InmaculadaPoza Guedes, PalomaSardón, OlaiaCorcuera, PaulaCruz, María J.González Barcala, Francisco J.Martínez Rivera, CarlosMullol, JoaquimMuñoz, XavierOlaguibel, José M.Plaza, VicenteQuirce, SantiagoValero, AntonioSastre, JoaquínKorta Murua, JavierPozo, Victoria delLorenzo Díaz, FabiánVillar, JesúsPino Yanes, MaríaAsthmaExacerbationsSERPINA1Alpha-1 antitrypsinAlpha-1 antitrypsin deficiencyhttps://portalciencia.ull.es/documentos/64860111a219857f1d78a011Introduction and objectives: Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether SERPINA1 genetic variants and reduced AAT protein levels are associated with asthma exacerbations. Materials and methods: In the discovery analysis, SERPINA1 Pi*S and Pi*Z variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (Open Targets Genetics) were analyzed. The associations between SERPINA1 Pi*S and Pi*Z variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates. Results: In the discovery, a significant association with asthma exacerbations was found for both Pi*S (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40–4.04, p-value=0.001) and Pi*Z (OR=3.49, 95%CI=1.55–7.85, p-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58–16.92, p-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57–0.91, p-value=0.005). The Pi*Z association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, p-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, p-value=0.007). Conclusions: AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.Bioquímica, Microbiología, Biología Celular y Genética202520252023info:eu-repo/semantics/articleapplication/pdfhttp://riull.ull.es/xmlui/handle/915/41776reponame:RIULL. Repositorio Institucional de la Universidad de La Lagunainstname:Universidad de La Laguna (ULL)InglésPulmonology (2023), 31 (1)Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ESoai:riull.ull.es:915/417762026-06-22T13:13:57Z
dc.title.none.fl_str_mv Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
title Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
spellingShingle Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
González Carracedo, Mario Andrés
Asthma
Exacerbations
SERPINA1
Alpha-1 antitrypsin
Alpha-1 antitrypsin deficiency
title_short Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
title_full Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
title_fullStr Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
title_full_unstemmed Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
title_sort Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations
dc.creator.none.fl_str_mv González Carracedo, Mario Andrés
Martín González, Elena
Hernández Pérez, José M.
Pérez Pérez, José A.
Pérez García, Javier
Herrera Luis, Esther
González Pérez, Ruperto
González González, Orelvis
Mederos Luis, Elena
Sánchez Machín, Inmaculada
Poza Guedes, Paloma
Sardón, Olaia
Corcuera, Paula
Cruz, María J.
González Barcala, Francisco J.
Martínez Rivera, Carlos
Mullol, Joaquim
Muñoz, Xavier
Olaguibel, José M.
Plaza, Vicente
Quirce, Santiago
Valero, Antonio
Sastre, Joaquín
Korta Murua, Javier
Pozo, Victoria del
Lorenzo Díaz, Fabián
Villar, Jesús
Pino Yanes, María
author González Carracedo, Mario Andrés
author_facet González Carracedo, Mario Andrés
Martín González, Elena
Hernández Pérez, José M.
Pérez Pérez, José A.
Pérez García, Javier
Herrera Luis, Esther
González Pérez, Ruperto
González González, Orelvis
Mederos Luis, Elena
Sánchez Machín, Inmaculada
Poza Guedes, Paloma
Sardón, Olaia
Corcuera, Paula
Cruz, María J.
González Barcala, Francisco J.
Martínez Rivera, Carlos
Mullol, Joaquim
Muñoz, Xavier
Olaguibel, José M.
Plaza, Vicente
Quirce, Santiago
Valero, Antonio
Sastre, Joaquín
Korta Murua, Javier
Pozo, Victoria del
Lorenzo Díaz, Fabián
Villar, Jesús
Pino Yanes, María
author_role author
author2 Martín González, Elena
Hernández Pérez, José M.
Pérez Pérez, José A.
Pérez García, Javier
Herrera Luis, Esther
González Pérez, Ruperto
González González, Orelvis
Mederos Luis, Elena
Sánchez Machín, Inmaculada
Poza Guedes, Paloma
Sardón, Olaia
Corcuera, Paula
Cruz, María J.
González Barcala, Francisco J.
Martínez Rivera, Carlos
Mullol, Joaquim
Muñoz, Xavier
Olaguibel, José M.
Plaza, Vicente
Quirce, Santiago
Valero, Antonio
Sastre, Joaquín
Korta Murua, Javier
Pozo, Victoria del
Lorenzo Díaz, Fabián
Villar, Jesús
Pino Yanes, María
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica, Microbiología, Biología Celular y Genética
dc.subject.none.fl_str_mv Asthma
Exacerbations
SERPINA1
Alpha-1 antitrypsin
Alpha-1 antitrypsin deficiency
topic Asthma
Exacerbations
SERPINA1
Alpha-1 antitrypsin
Alpha-1 antitrypsin deficiency
description https://portalciencia.ull.es/documentos/64860111a219857f1d78a011
publishDate 2023
dc.date.none.fl_str_mv 2023
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://riull.ull.es/xmlui/handle/915/41776
url http://riull.ull.es/xmlui/handle/915/41776
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Pulmonology (2023), 31 (1)
dc.rights.none.fl_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
rights_invalid_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIULL. Repositorio Institucional de la Universidad de La Laguna
instname:Universidad de La Laguna (ULL)
instname_str Universidad de La Laguna (ULL)
reponame_str RIULL. Repositorio Institucional de la Universidad de La Laguna
collection RIULL. Repositorio Institucional de la Universidad de La Laguna
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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